A Phase I Dose Escalation Study With Sunitinib (SutentR) in Combination With Capecitabine and Irinotecan (Capiri) in Previously Treated Patients With Advanced Colorectal Cancer
- Histological proof of colorectal cancer
- Patients should have failed one previous line of systemic treatment for advanced
disease (and not more than one treatment line), either with fluoropyrimidine
monotherapy or in combination with oxaliplatin and/or bevacizumab.
- No prior treatment with irinotecan or sunitinib
- Age ≥ 18 years
- WHO PS 0-1 (see Appendix 3, corresponding with Karnofsky ≥ 70% )
- Life expectancy ≥ 12 weeks
- Written informed consent
- No measurable disease according to RECIST criteria.
- Prior anti-cancer therapy < 3 weeks before first dose. For cetuximab < 30 days or
bevacizumab < 60 days prior to the first dose.
- Unresolved toxicity > CTC gr 1 from previous anti-cancer therapy (including
radiotherapy) except for alopecia.
- Inadequate bone marrow function (Hb ≤ 5.6 mmol/L, absolute neutrophil count (ANC) ≤
1.5 x 109/L, platelets ≤100 x 109/L)
- renal dysfunction (serum creatinine ≥ 1.5x ULN and glomerular filtration rate ≤ 50
- Prothrombin time (PT) and activated partial thromboplastin time (APTT) > 2x ULRR
- Hepatic dysfunction (serum bilirubin ≥ 1.5x ULN, serum transaminases ≥ 2.5 x ULN)
- Greater than +1 proteinuria on two consecutive dipsticks taken no less then 2 weeks
apart unless urinary protein < 1,5 g in a 24 Hr period.
- Pregnant or lactating women
- History of clinical signs/symptoms of CNS metastases
- Previous intolerance of fluoropyrimidine therapy, known dihydropyrimidine
dehydrogenase (DPD) deficiency. Known hypersensitivity to irinotecan or sunitinib of
- No major surgery < 4 weeks prior to study entry.
- No radiotherapy < 4 weeks prior to study entry except for palliative radiotherapy at
- Any evidence of concurrent severe or uncontrolled disease (i.e. uncontrolled
hypertension, congestive heart failure, myocardial infarction < 6 months, chronic
active infection, poorly regulated diabetes mellitus)
- Any previous significant cardiovascular event during previous fluoropyrimidine
myocardial ischemia or infarction, arterial thrombosis, pulmonary emboli)
- Mean Qtc with Bazetts correction > 470 msec in screening ECG, or a history with
familial long QT syndrome
- Significant haemorrhage (>30 ml bleeding/episode in the last 3 months) or haemoptysis
(>5 ml fresh blood in previous 4 weeks)
- History of impairment of gastrointestinal function or -disease that may significantly
impair the absorption of oral drugs (i.e. uncontrolled nausea, vomiting, diarrhoea,
malabsorption syndrome, bowel obstruction, or inability to swallow tablets)
- Any psychological, familial, sociological or geographical condition potentially
hampering compliance with the study protocol and follow-up schedule; those conditions
should be discussed with the patient before registration in the trial
- Concomitant use medication that may significantly affect hepatic cytochrome P450 drug
metabolizing activity by way of enzyme induction or inhibition < 2 weeks if the first
dose and throughout the study period (see Appendix 2)
- Other concomitant anti-cancer therapy.